Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain

Liu, Ming; Xie, Zhongjian; Costello, Christie A.; Zhang, Weidong; Chen, Liujun; Qi, Dake; Furey, Andrew; Randell, Edward; Rahman, Proton; Zhai, Guangju

doi:10.1097/j.pain.0000000000002052

Cited by 20 publications

(29 citation statements)

References 77 publications

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“…The ratio of LPC to PC has been reported to be associated with inflammation in severe OA and RA [ 43 , 44 ]. Consistent with one previous cross-sectional study [ 22 ], no association between the ratio of LPC to PC and MSMP was observed in the current study. Furthermore, our longitudinal analysis found no associations between ratio of LPC to PC and persistent MSMP.…”

Section: Discussionsupporting

confidence: 93%

“…There are, to date, two studies from our group identifying MSMP-associated metabolites. We found that two bioactive proinflammatory lipid compounds, LPC (26:0 and 28:1), were positively associated with MSMP using the extreme phenotype sampling strategy [ 22 ]. More recently, we identified and replicated the association between an elevated SM C18:1 level and the presence of MSMP in two independent cohorts using different criteria of MSMP [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our recent study identified and replicated one lipid (i.e., sphingomyelin (SM) C18:1) associated with the presence of MSMP in two independent cohorts [ 21 ]. In addition, two proinflammatory lipid compounds in association with the presence of MSMP were also identified [ 22 ]. This may reflect that dysfunction in lipid metabolism is involved in the MSMP initiation.…”

Section: Introductionmentioning

confidence: 99%

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Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain

Liu

Tian

et al. 2022

Metabolites

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Objective: Lipid mediators have been suggested to have a role in pain sensitivity and response; however, longitudinal data on lipid metabolites and persistent multisite musculoskeletal pain (MSMP) are lacking. This study was to identify lipid metabolic markers for persistent MSMP. Methods: Lipidomic profiling of 807 lipid species was performed on serum samples of 536 participants from a cohort study. MSMP was measured by a questionnaire and defined as painful sites ≥4. Persistent MSMP was defined as having MSMP at every visit. Logistic regression was used with adjustment for potential confounders. The Benjamini–Hochberg method was used to control for multiple testing. Results: A total of 530 samples with 807 lipid metabolites passed quality control. Mean age at baseline was 61.54 ± 6.57 years and 50% were females. In total, 112 (21%) of the participants had persistent MSMP. Persistent MSMP was significantly associated with lower levels of monohexosylceramide (HexCer)(d18:1/22:0 and d18:1/24:0), acylcarnitine (AC)(26:0) and lysophosphatidylcholine (LPC)(18:1 [sn1], 18:2 [sn1], 18:2 [sn2], and 15-MHDA[sn1] [104_sn1]) after controlling for multiple testing. After adjustment for age, sex, body mass index, comorbidities, and physical activity, HexCer(d18:1/22:0 and d18:1/24:0) and LPC(15-MHDA [sn1] [104_sn1]) were significantly associated with persistent MSMP [Odds Ratio (OR) ranging from 0.25–0.36]. Two lipid classes—HexCer and LPC—were negatively associated with persistent MSMP after adjustment for covariates (OR = 0.22 and 0.27, respectively). Conclusions: This study identified three novel lipid signatures of persistent MSMP, suggesting that lipid metabolism is involved in the pathogenesis of persistent pain.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain

Liu

Tian

et al. 2022

Metabolites

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“…AAs could prove to be metabolites of several beneficial interventions, as they can modulate immune responses and, for instance, arginine is required for normal proliferation and maturation of T-cells, and it is involved in the macrophage class transition from M1 to M2, driving inflammation and resolution [ 66 ]. Bile acids [ 67 ] and pro-inflammatory LPCs [ 68 ] represent other metabolites that can be related to chronic pain and should be studied in more detail regarding joint diseases.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis or Rheumatoid Arthritis

et al. 2022

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Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch’s t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.

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“… 12 In contrast, the current investigation is designed to minimize the conundrums apparent in previous studies of meditation and CVD by implementing an extreme phenotype sampling strategy, which has been used successfully in both genetic and metabolomic studies. 13 , 14 Specifically, we recruited 78 Tibetan Buddhist monks who engaged in meditation practice for a remarkable average of 19 years. The monks engaged in at least one hour per day of mediation with a mean time of 3.92 ± 3.21 h (range 1–15 h).…”

Section: Introductionmentioning

confidence: 99%

The heart-brain axis: A proteomics study of meditation on the cardiovascular system of Tibetan Monks

Xue

Chiao

et al. 2022

eBioMedicine

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Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain

Abstract: Supplemental Digital Content is Available in the Text. Metabolic profiling coupled with extreme sampling identified lysophosphatidylcholines 26:0 and 28:1 to be potential biomarkers for multisite musculoskeletal pain.

Cited by 20 publications

References 77 publications

Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain

Lipidomic Profiling Identifies Serum Lipids Associated with Persistent Multisite Musculoskeletal Pain

Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis or Rheumatoid Arthritis

The heart-brain axis: A proteomics study of meditation on the cardiovascular system of Tibetan Monks

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